NUJHS Vol. 3, No.4, December 2013, ISSN 2249-7110 Nitte University Journal of Health Science Original Article : IT'S ROLE IN ORAL AND SYSTEMIC HEALTH Harini K.1 , Subash Babu2 , Vidya Ajila3 & Shruthi Hegde4 1Senior Lecturer, Department of Periodontics, 2 Professor & HOD, 3 Reader, 4 Senior Lecturer, Department of Oral Medicine & Radiology, A.B. Shetty Memorial Institute of Dental Sciences, Nitte University, Deralakatte, Mangalore - 575 018, India. Correspondence : Harini K. Senior Lecturer, Department Of Periodontics, A.B. Shetty Memorial Institute of Dental Sciences, Nitte University, Mangalore 575018. Karnataka, India. Mobile : +91 97431 99994 E-mail : [email protected] Abstract: A range of treatment modalities are available for the treatment of different oral diseases.The frequent use and misuse of currently available therapeutic agents has led to the evolution of increased incidence of adverse effects and development of resistant strains. Hence the search for an alternative option continues. Medicinal plants have been used as traditional treatment agents since ages. Garlic ( sativum) has been recognized for a number of therapeutic properties in the traditional system of medicine. Allium sativum is traditionally employed to treat infection, colds, diabetes, heart disease, and a host of other disorders. Clinically, it has been evaluated for lowering blood pressure, cholesterol, and glucose concentration, as well as for the prevention of arteriosclerosis and cancer. It is well known for its potent anti- inflammatory, anti- oxidant, anti-bacterial and antimutagenic properties. This article aims to review the efficacy of garlic in maintaining oral health in particular and overall health in general. Key words: Garlic, Allium Sativum, P. gingivalis, Cardiovascular diseases.

Introduction : compromised individuals and financial considerations in Oral diseases qualify as major public health problems developing countries there is considerable interest in the owing to their high prevalence and incidence in all regions development of alternative prevention and treatment of the world. An adverse oral health condition affects three options and products for oral diseases.3, 4 Traditional plants aspects of daily living: 1) systemic health, 2) quality of life, and natural phytochemicals can treat bacterial infections and 3) economic productivity. Numerous studies have and are considered as good alternatives to synthetic suggested that there is a strong association between oral chemicals.5 Numerous traditional medicinal plants have health and systemic health.1 In developed countries 10% of been evaluated for their potential application in the public health expenditure is related to curative dental care. prevention or treatment of oral diseases. Garlic is one of Whereas in most developing countries, expenditure to oral the most extensively investigated medicinal plants since health care is very low; limited access to dental healthcare ancient times. With its high trace mineral content and is generally restricted to emergency dental care or pain enzymes, sulfur containing compounds, garlic has shown relief. While there has been a marked improvement in oral anti-viral, anti-bacterial, anti-fungal and antioxidant health in most developed countries, it is deteriorating in abilities. Garlic extract has been shown to have a wide developing countries spectrum inhibitory effect on the growth of various gram- specially among children positive and gram-negative bacteria and is also active Access this article online Quick Response Code from low socio-economic against multi-drug resistant organisms such as status.2 With the rise in Pseudomonas aeruginosa, Klebsiella pneumonia, and disease incidence, Mycobacterium tuberculosis.6 resistant pathogenic Here, we review the clinically relevant effects of garlic, bacteria, opportunistic focusing on potential mechanisms involved in the response infections in immune to garlic and the potential clinical implications associated

Keywords : Garlic, Allium Sativum, P. gingivalis, Cardiovascular diseases. 17 - Harini K. NUJHS Vol. 3, No.4, December 2013, ISSN 2249-7110 Nitte University Journal of Health Science

with its consumption. l Anti fungal

l Anti oxidant Garlic is a perennial plant with white, starry flowers and l Anti cancer, bulb clusters of individual teardrop shaped cloves encased l Anti aging effects in dry skin-like papers that unite to create the bulb. The l Reduction of risk factors for cardiovascular diseases garlic bulb is the part of the plant most often used as l Restoration of physical strength flavoring agent and medicinal herb. Garlic can be eaten l Resistance to various stresses raw, chopped, minced, or juiced. It has a characteristic l Stimulation of immune function. pungent, spicy flavor that mellows and sweetens considerably with cooking. Garlic otherwise known as Chemistry of Garlic : Allium sativum, is a species in the genus from The chemistry of garlic is quite complex and clinical Liliaceae family. Garlic is grown globally, but China is by far pharmacological properties of garlic have been extensively the largest producer of garlic followed by India, South studied. Whole garlic cloves are intact bulbs that contain an Korea, Spain, and the United States. odorless, sulfur-containing amino acid derivative, a covalently bonded compound with the chemical formula Historical Perspective : C6 H 11 NO 3 S(Figure 1). The primary sulfur-containing For thousands of years, garlic has been used throughout constituents in whole, intact garlic are the ? glutamyl the world as a medicine. Sanskrit records, from cysteines and S allyl cysteine sulfoxides, including alliin.7 approximately 5000 years ago, describe the use of garlic remedies. Chinese, Egyptian, and Greek documents from When the bulb is crushed or cut, alliin is altered by the Hippocrates, Aristotle and Pliny cite numerous therapeutic enzyme, alliinase and is converted into . Allicin uses for garlic. In 1844 Theodor Wertheim, a German (C6 H 10 OS 2 ) is an oily, yellow liquid that gives garlic its chemist, distilled a pungent substance from garlic and characteristic odor. (Figure 2) called it allyl, the Latin name for garlic. Four years later, Typical volatiles in crushed garlic and garlic essential oil Louis Pasteur in Paris showed that allyl could inhibit the include diallyl sulfide (DAS), (DADS), diallyl growth of bacteria. This was a great discovery because 150 trisulfide, methyl allyl disulfide, methyl allyl trisulfide, 2- years ago, doctors had nothing to eradicate bacteria. The vinyl-1,3- dithiin, 3-vinyl-1,2-dithiin (Fenwick and Hanley Babylonians, Egyptians, Phoenicians, Vikings, Chinese, 1985) and ajoene (Block et al. 1984). At the same time, ? Greeks, Romans and Hindus have adopted a number of glutamylcysteines are converted to S-allylcysteine (SAC) via therapeutic uses for this botanical (Murray 2005).Garlic a pathway other than the alliin/allicin pathway. SAC was used as a remedy for intestinal disorders, flatulence, contributes heavily to the health benefits of garlic. worms, respiratory infections, skin diseases, wounds, symptoms of aging and many other ailments. Garlic thus Mechanism of action of Garlic : acquired a reputation in the folklore; modern science has Broadly the mechanisms of action of garlic in oral health created a large and fast growing body of scientific research care are: its role as a strong antioxidant, antibacterial, 7 on this medicinal herb. antiseptic and immune - modulatory effect.7

To date thousands of scientific articles from all over the Antimicrobial activity of garlic against oral bacteria : world have gradually confirmed the traditionally Cavallito and Bailey 8 confirmed that allicin is primarily recognized health benefits of garlic. Biological responsible for the antimicrobial action of garlic. Its main 7 responses of garlic include mechanism of action is by blocking thiol-containing l Anti bacterial enzymes, including cysteine proteases and alcohol l Anti viral

Keywords : Garlic, Allium Sativum, P. gingivalis, Cardiovascular diseases. 18 - Harini K. NUJHS Vol. 3, No.4, December 2013, ISSN 2249-7110 Nitte University Journal of Health Science dehydrogenases.9, 10 Cysteine proteinase enzymes are Due to unidentified reasons, it was assumed that among the main culprits in infection, providing infectious penetration of allicin into the bacteria was restrained by organisms with the means to damage and invade tissues. hydrophilic capsular or mucoid layers.15 Alcohol dehydrogenase enzymes play a major role in these Antioxidant effects of Garlic : harmful organisms' metabolism and survival. Oxidative stress is recognized as one of the pathogenic The active component of garlic extract, allicin partially mechanisms of chronic inflammatory diseases, including inhibits DNA and protein synthesis, and entirely inhibits cardiovascular disorders and cancer. Consequently, RNA synthesis. compounds with antioxidant properties may be used to prevent oxidative stress-mediated diseases.16 Garlic extract has shown to have a wide spectrum of antibacterial activity, including effects on, Staphylococcus, Abundant research has established garlic and its Streptococcus, Klebsiella, Escherichia, Salmonella, organosulfur compounds to be strong antioxidants. Garlic Proteus, Clostridium, Mycobacterium and Helicobacter protection against oxidant induced damage can be species.9, 10 credited to major compounds in garlic extract like S- allycysteine (SAC) and S-allylmercapto-L-cysteine, by Groppo FC et al 11 demonstrated that a mouth wash displaying radical scavenging activity and modulating containing garlic extract was more effective at reducing the cellular antioxidant enzyme activity. total salivary bacterial count and the streptococcal mutans count. Antioxidant properties of garlic have been demonstrated in animal disease models. Aqueous garlic extract reduces Ghannoum MA 12 described marked inhibitory effect of oxidative stress and prevents vascular remodeling by garlic against C. albicans. suppressing NAD(P)H-oxidase in the fructose-induced 17 Bakri IM 13 reported that garlic extract was slow and less metabolic syndrome model in rats. active against oral Gram-positive species when compared SAC also reduces lipid peroxidation and superoxide radical to a range of Gram-negative species. This difference production, and elevates Cu-Zn-superoxide dismutase between gram negative and gram positive organisms is due activity in 1-methyl-4-phenylpyridinium-induced to inability of garlic extract to invade the thick Parkinsonism in mice. 18 peptidoglycan layer in the Gram positive cell envelope. In recent years, numerous human intervention studies Garlic extract was sensitive particularly to P.gingivlais, have examined the antioxidant influence of garlic in P.Intermedia, A. actinomycetemcomitans, F. nucleatum humans. Imai and coworkers19 studied the antioxidant and had lower minimum inhibitory concentration ( MICs) properties of three garlic preparations and organosulfur and minimum bactericidal concentration (MBCs) than the compounds and observed that aged garlic extract exhibited other gram negative organisms tested. Trypsin like activity radical scavenging activity protecting endothelial cells and total protease activity are almost completely inhibited from injury by oxLDL. by garlic extract, apparently through allicin's affinity for thiol groups. 10 Dhawan V 20 reported reduced oxLDL and 8-iso- prostaglandin F2 alpha levels, accompanied by a significant According to some investigators garlic was effective against reduction in both systolic and diastolic blood pressure in antibiotic resistant organisms.14 On the other hand; some hypertensive patients on two months of garlic oil investigators have demonstrated that certain mucoid supplementation. bacterial strains were discovered to be resistant to allicin.

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These results suggest that garlic has potent antioxidant against human cytomegalovirus, influenza virus type 3, activity in delaying the onset and development of chronic vaccine virus, vesicular stomatitis virus and human inflammatory diseases, including cardiovascular disorders, rhinovirus type 2.23 diabetes cancer, and neurodegenerative diseases caused Antifungal activity : by an imbalance between free radical production and Bakri IM 13 et al confirmed the antifungal activity of garlic antioxidant defenses. against C. albicans described by Ghannoum MA .12 Ledezma Immunomodulatory Effects : et al 24 demonstrated that ajoene , an active compound in Sufficient evidences suggest that garlic may have garlic may play a role as a topical fungal agent . significant enhancing effects on the immune system. Antimutagenic effects : Extensive studies are conducted on animals, in vitro and in Garlic has known to possess anticancer activity because of vivo. However, the human studies that have been its various effects on biological pathways. These include conducted are encouraging. free radical scavenging, inhibition of mutagenesis and Abdullah TH et al 21 demonstrated positive effects on effects on cell proliferation and tumor growth. Garlic and immunoreactions and increase in the percentage of its organosulphur compounds modulate the activity of phagocytosing peripheral granulocytes and monocytes on several metabolising enzymes that activate (cytochrome using an alliin standardised garlic powder preparation. P450s) or detoxify (glutathione S-transferases) carcinogens Another human study conducted on AIDS patients with an and inhibit the formation of DNA adducts in several target unrefined garlic extract (5-10 g/day) demonstrated a major tissues. 25 Numerous studies have established the role of increase in the percentage of natural killer cell activity.21 garlic in cancer prevention particularly in relation to digestive tract cancers, including esophageal and stomach Anti-inflammatory : cancers. 26 Agarwal et al 22 demonstrated suppression of the nuclear factor-kappaB activation pathway and inflammatory Cardiovascular effects : prostaglandins thus establishing anti-inflammatory activity Garlic's protective effects on cardiovascular system of garlic. include:

l Inhibition of hepatic hydroxymethyl glutaryl-CoA Therapeutic applications in dentistry : reductase activity by alliin and allicin and reduction in This potent anti- inflammatory, antioxidant, antibacterial LDL-cholesterol. 26 effect and immunomodulatory effect of garlic suggest that l Inhibition of platelet aggregation due to suppression of it has a therapeutic potential in different oral diseases. intraplatelet Ca2þ mobilization, an increase in cyclic Garlic produced a significant reduction in the inflammatory AMP and cyclic GMP levels, an increase in platelet- infiltrate and potentially inhibited innate immune derived nitric oxide production, and a reduction in response associated with periodontal diseases thus platelet binding to fibrinogen. 28 suggesting a therapeutic potential in this chronic inflammatory condition. Garlic can be used as a mouth Drug interactions : wash, sub gingival irrigant and as a component in local drug Few authors have suggested that garlic affects the drug delivery system. It has a great role in the treatment of metabolism and alters their pharmacokinetics. It has been periodontal diseases. hypothesized that garlic organosulfur compounds may be able to prevent glutathione depletion, a compound Other therapeutic applications of garlic : necessary for liver detoxification. Sabayan et al 29 Antiviral activity : demonstrated that garlic provides protection against Many investigators have demonstrated antiviral activity

Keywords : Garlic, Allium Sativum, P. gingivalis, Cardiovascular diseases. 20 - Harini K. NUJHS Vol. 3, No.4, December 2013, ISSN 2249-7110 Nitte University Journal of Health Science reactive oxygen species-induced stress on liver function. Figure 1: Chemical structure of intact garlic H H O Sener et al 30 showed that aged garlic can reverse oxidant H H H

effects of nicotine toxicity in rats. Maldonado et al 31 CCCS CCC H showed that aged garlic extract, do not interfere with the H H S HH antibiotic activity of gentamycin but may improve gentamycin -induced nephrotoxicity. However, as results Figure 2: Chemical changes of crushed garlic remain inconsistent and contradictory more well-designed Allium Sativum studies are necessary to clarify whether garlic affects the metabolism of drugs and alters their pharmacokinetics. y- Dlutamyl cysteine Alliin Adverse effects : Garlic is generally considered safe but a commonly On rupture associated side effect with garlic intake is halitosis, especially when raw forms of the herbs are used. However, Allinase Mitchell 32 reported that the odor is decreased when garlic S- allyl cysteine (SAC) ALLICIN is taken before meals. Odorless garlic formulations are available. However, odorless garlic is often prepared either References by adding chemical substances to mask the odor or by 1. P. E. Petersen. The burden of oral disease: challenges to improving oral cooking the garlic, which may destroy some of the active health in the 21st century. Bulletin of the World Health Organization 2005 ;83: 3. ingredients. Other side effects include nausea and gastric 2. L. M. Jamieson, E. J. Parker, and J. M. Indigenous child oral health at a regional and state level. Journal of Paediatrics and Child Health 2007; irritation. Although rare, garlic allergy has been attributed 43: 117–121. to the protein alliin lyase, which has induced IgE mediated 3. Tichy J, Novak J. Extraction, assay, and analysis of antimicrobials from plants with activity against dental pathogens (Streptococcus sp.) J 33 hypersensitivity responses from skin prick testing . Altern Complement Med 1998;4: 39 – 45. 4. Badria FA, Zidan OA. Natural products for dental caries prevention. J Saw et al 34 warned not to use garlic while on anticoagulant Med Food 2004; 7: 381 – 384. 5. G. R. Prabu, A. Gnanamani, and S. Sadulla .Guaijaverin — A plant therapy as garlic has been associated with decreased flavonoid as potential antiplaque agent against Streptococcus mutans. J Appl Microbiol 2006;101:487–495. platelet aggregation and bleeding events. 6. Fani MM, Kohanteb J, Dayaghi M. Inhibitory activity of garlic (Allium sativum) extract on multidrug-resistant Streptococcus mutans. J Conclusion : Indian Soc Pedodont Prev Dent 2007; 25: 164 – 168. 7. Amagase H, Petesch BL, Matsuura H, Kasugai S and Itakura Y. Recent Over the years, garlic has been a part of tradition, ancient Advances on the Nutritional Effects Associated with the Use of Garlic myth, and household remedies. The therapeutic as a Supplement. J. Nutr 2001; 131: 955–962. 8. Block E. The chemistry of garlic and . Sic Am 1985; 252: 114– properties of garlic have been known to mankind for ages. 119. 9. Ankri S, Miron T, Rabinkov A, Wilechek M, Mirelman D. Allicin from Garlic and its compounds have been found to attack garlic strongly inhibits cysteine proteinases and cytophathic effects of multiple targets, which provide the basis for their Entamoeba histolytica. Antimicrob Agents Chemother 1997;41: 2286—8. effectiveness in many different diseases. However, the 10. Rabinkov A, Miron T, Konstantinovski L, Wichek M, Mirelman D, Weiner L. The mode of action of allic: trapping of radicals and results observed in human clinical and intervention studies interaction with thiol-containing proteins. Biochim Biophys Acta have been inconsistent and the risk of garlic drug 1998;1379: 233—44. 11. Groppo FC, Ramacciato JC, Simoes RP, Florio FM, Sartoratto A. interactions is attracting increasing interest. Therefore Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against further experiments are necessary to recognize the oral microorganisms. Int Dent J 2002; 52:433—7. 12. Ghannoum MA. Inhibition of Candida adhesion to buccal epithelial definite health benefits and impact of garlic. By looking cells by an aqueous extract of Allium sativum (garlic). J Appl Bacteriol 1990; 68: 163—9. back into history we can apply some old world uses of garlic 13. Bakri IM, Douglas CWI. Inhibitory effect of garlic extract on oral for new ways to improve oral and overall health. bacteria. Arch of Oral Biol 2005; 50: 645—651. 14. Sivam GP. Protection against Helicobacter pylori and other bacterial infection by garlic. J Nutr 2001;131: 1106 – 1108.

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